A Study Evaluating the Safety of VX-152 Combination Therapy in Adults With Cystic Fibrosis
- Conditions
- Cystic Fibrosis
- Interventions
- Registration Number
- NCT02951195
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
This is a Phase 2, randomized, double blind, placebo and active-controlled, parallel group, multicenter study designed to evaluate the safety and tolerability of VX-152 in Triple Combination (TC) with tezacaftor (TEZ; VX-661) and ivacaftor (IVA; VX-770) in subjects with cystic fibrosis (CF) who are heterozygous for the F508del mutation and a minimal function (MF) CFTR mutation not likely to respond to TEZ and/or IVA therapy (F508del/MF), or who are homozygous for the F508del mutation of the CF transmembrane conductance regulator (CFTR) gene (F508del/F508del).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 80
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Willing and able to comply with scheduled visits, treatment pan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
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Body weight ≥35 kg.
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Sweat chloride value ≥ 60 mmol/L from test results obtained during screening.
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Subjects must have an eligible CFTR genotype:
- Cohorts 1A, 1B, 1C: Heterozygous for F508del and a minimal function mutation known or predicted not to respond to TEZ and/or IVA.
- Cohorts 2A, 2B: Homozygous for F508del.
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Subjects must have an FEV1 ≥40% and ≤90% of predicted normal for age, sex, and height at the Screening Visit.
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Stable CF disease as judged by the investigator.
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Willing to remain on a stable CF medication regimen through the planned end of treatment or if applicable the Safety Follow-up Visit.
- History of any comorbidity that in the opinion of the investigator might confound the results of the study or pose an additional risk in administering study drug to the subject.
- History of cirrhosis with portal hypertension.
- Risk factors for Torsade de Pointes.
- History of hemolysis.
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency assessed at Screening.
- Clinically significant abnormal laboratory values at screening.
- An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy for pulmonary disease within 28 days before the first dose of study drug.
- Lung infection with organisms associated with a more rapid decline in pulmonary status.
- An acute illness not related to CF within 14 days before the first dose of study drug.
- A standard digital ECG demonstrating QTc >450 msec at screening.
- History of solid organ or hematological transplantation.
- History or evidence of cataract or lens opacity determined to be clinically significant by the ophthalmologist or optometrist, based on the ophthalmologic examination during the Screening Period.
- History of alcohol or drug abuse in the past year, including but not limited to, cannabis, cocaine, and opiates, as deemed by the investigator.
- Ongoing or prior participation in an investigational drug study with certain exceptions.
- Use of commercially available CFTR modulator within 14 days before screening (applies only to Cohorts 1A, 1B, and 1C).
- Pregnant or nursing females: Females of childbearing potential must have a negative pregnancy test at screening and Day 1.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 2 Cohort 2A: TC VX-152 - Part 2 Cohort 2A: TEZ/IVA Placebo - Part 1: Placebo Placebo - Part 1 Cohort 1A: TC VX-152 - Part 1 Cohort 1A: TC TEZ/IVA - Part 1 Cohort 1A: TC IVA - Part 1 Cohort 1B: TC VX-152 - Part 1 Cohort 1B: TC TEZ/IVA - Part 1 Cohort 1B: TC IVA - Part 1 Cohort 1C: TC VX-152 - Part 1 Cohort 1C: TC TEZ/IVA - Part 1 Cohort 1C: TC IVA - Part 2 Cohort 2A: TEZ/IVA TEZ/IVA - Part 2 Cohort 2A: TEZ/IVA IVA - Part 2 Cohort 2A: TC TEZ/IVA - Part 2 Cohort 2A: TC IVA - Part 2 Cohort 2B: TEZ/IVA TEZ/IVA - Part 2 Cohort 2B: TEZ/IVA IVA - Part 2 Cohort 2B: TEZ/IVA Placebo - Part 2 Cohort 2B: TC VX-152 - Part 2 Cohort 2B: TC TEZ/IVA - Part 2 Cohort 2B: TC IVA -
- Primary Outcome Measures
Name Time Method Safety and Tolerability as Assessed by Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Day 1 Through Safety Follow-up Visit (Up to Day 43 for Part 1 and Day 71 for Part 2) Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 15 for Part 1 and Part 2 Cohort 2A From Baseline at Day 15 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Absolute Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B From Baseline Through Day 29 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
- Secondary Outcome Measures
Name Time Method Absolute Change in Sweat Chloride Concentrations at Day 15 for Part 1 and Part 2 Cohort 2A From Baseline at Day 15 Sweat samples were collected using an approved collection device.
Absolute Change in Sweat Chloride Concentrations Through Day 29 for Part 2 Cohort 2B From Baseline Through Day 29 Sweat samples were collected using an approved collection device.
Relative Change in ppFEV1 at Day 15 for Part 1 and Part 2 Cohort 2A From Baseline at Day 15 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Relative Change in ppFEV1 Through Day 29 for Part 2 Cohort 2B From Baseline Through Day 29 FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration.
Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score at Day 15 for Part 1 and Part 2 Cohort 2A From Baseline at Day 15 The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Absolute Change From Baseline in CFQ-R Respiratory Domain Score at Day 29 for Part 2 Cohort 2B From Baseline at Day 29 The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life.
Pre-dose Plasma Concentration (Ctrough) of VX-152, TEZ, M1-TEZ, IVA, and M1-IVA Pre-dose at Day 8, Day 15 and Day 29